A tooth whitening composition having a phased, synergistic release and a method of making the same

Abstract

A teeth whitening composition with phased synergistic release and its preparation method are disclosed. The composition comprises: an enzymatic membrane-degrading component, a chelating desorption component, a porous adsorbent material, an enamel repair material, a friction matrix, a first porous carrier (pore size 50-100 nm), a second porous carrier (pore size 2-20 nm), a surfactant, a sweetener, and a flavoring. The enzymatic membrane-degrading component is loaded onto the first porous carrier, and the chelating desorption component is loaded onto the second porous carrier. The three-stage release is achieved through the difference in pore size: in the first stage (0-1 min), the enzymatic component rapidly decomposes the acquired membrane; in the second stage (2-3 min), the chelating component cleaves the pigment-binding bonds; and in the third stage (after 2 min), the adsorbent and repair materials adsorb the pigment and repair the enamel. This invention achieves highly efficient stain removal, low damage, long-lasting whitening, and low restaining rate through the synergistic and phased release of enzymatic hydrolysis, chelation, adsorption, and repair.

Description

Technical Field

[0001] This invention relates to the field of oral care technology, and more specifically, to a teeth whitening composition with a phased synergistic release function and its preparation method. Background Technology

[0002] With the improvement of people's living standards and the enhancement of aesthetic awareness, teeth whitening has become an important development direction in the field of oral care. Daily dietary factors such as coffee, tea, red wine, and tobacco can easily cause extrinsic pigment deposition on the tooth surface, leading to yellowing or darkening of teeth and affecting their appearance.

[0003] Studies have shown that the formation of extrinsic tooth pigmentation typically involves multiple stages: First, proteins in saliva form an acquired film on the tooth surface, providing a matrix for pigment adhesion; subsequently, pigment molecules bind to the tooth surface through electrostatic interactions, hydrogen bonds, and calcium ion bridging; furthermore, the microporous structure and roughness of the enamel surface further promote pigment deposition and re-staining. Therefore, tooth staining is a complex process involving organic film formation, inorganic binding, and changes in surface structure.

[0004] In existing technologies, teeth whitening products mainly employ single mechanisms such as mechanical friction, chemical chelation, enzymatic stain removal, physical adsorption, or peroxide bleaching, but each has its own limitations. In recent years, some literature has begun to explore combining multiple mechanisms, for example:

[0005] Chinese patent CN112043622A discloses a whitening toothpaste containing enzymes and bioactive glass. It comprises bromelain, papain, lysozyme, and bioactive glass, claiming to achieve whitening through a triple mechanism of enzymatically breaking down pigment deposits, inhibiting deposit regeneration, and promoting enamel remineralization. However, this technology lacks a chelation and desorption mechanism for firmly bound pigments, does not include porous adsorption materials, and does not design the sequential release of each component. When the enzyme and the repair material act simultaneously, the enzyme's effect may be affected by the physical barrier of the repair material, resulting in limited synergistic efficiency.

[0006] International patent application US20180289606A1 discloses a multilayer membrane delivery system that achieves the stepwise action of whitening agents and remineralizing agents through a first soluble membrane and a second membrane. Although this technology is similar to this application in its "stepwise action" concept, its core whitening agent is still a peroxide-based bleaching agent, which poses a risk of causing tooth sensitivity and oral irritation. Furthermore, its release sequence is controlled by the physical dissolution rate of the multilayer membrane, making the preparation process complex and its application limited to membrane formulations, making it unsuitable for everyday toothpaste or tooth powder products.

[0007] Furthermore, Chinese patent CN105142596A discloses an oral composition containing a protease and a soluble calcium phosphate remineralizing agent, and relates to a bilayer tablet scheme (rapidly disintegrating layer + slowly eroding layer) to achieve staged release. However, the staged release of this technology relies on the difference in disintegration and erosion rates of the tablets and is limited to tablet dosage forms; it also does not include a chelation desorption system or porous adsorption materials, and its ability to remove pigments that are firmly bound by calcium ion bridging is insufficient.

[0008] In summary, while existing technologies have recognized the importance of multi-mechanism combinations and phased effects, none have fully covered the complete synergistic chain of "enzymatic membrane breakdown—chelation desorption—adsorption repair," nor have they employed a porous carrier loading strategy based on pore size differences to achieve a simple, stable, and time-sequential release suitable for powder / paste systems. Furthermore, most technologies still rely on peroxide bleaching or lack consideration for enamel repair functions, resulting in limited whitening effects, easy restaining, or safety risks. Therefore, developing a whitening composition that comprehensively targets the pigment formation mechanism, achieves efficient stain removal through phased synergistic effects, and also possesses enamel repair functions has significant technical and application value. Summary of the Invention

[0009] This invention aims to overcome the shortcomings of existing technologies and provide a teeth whitening composition with a staged synergistic release function and its preparation method. This composition achieves a highly efficient, gentle, and long-lasting whitening effect through the synergistic effects of enzymatic membrane desorption, chelation desorption, and adsorption repair.

[0010] To achieve the above objectives, the present invention provides the following technical solution:

[0011] A teeth whitening composition with phased synergistic release, comprising, by weight percentage, the following components:

[0012] Enzymatic membrane desorption component: 0.5% - 2%; Chelating desorption component: 0.5% - 5%; Porous adsorbent material: 5% - 10%; Enamel restoration material: 5% - 10%; Friction matrix: 45% - 65%; First porous carrier (pore size 50-100 nm): 5% - 10%; Second porous carrier (pore size 2-20 nm): 5% - 10%; Surfactant: 3% - 5%; Sweetener: 5% - 10%; Flavoring: 0.5% - 2%.

[0013] The enzymatic membrane-degrading component is loaded onto a first porous support; the chelating desorption component is loaded onto a second porous support. The porous adsorption material and the enamel restoration material are non-loaded particles and remain continuously in the system during use.

[0014] Furthermore, the specific surface area of ​​the first porous carrier is 30-150 m². 2 / g, pore volume 0.8-1.5 cm³ 3 / g; the specific surface area of ​​the second porous carrier is 600-1000 m². 2 / g, pore volume 0.5-1.0 cm³ 3 / g.

[0015] Furthermore, the enzymatic membrane-degrading component is selected from one or more combinations of papain, bromelain, and lysozyme, with an enzyme activity retention rate of ≥85%.

[0016] Furthermore, the chelating and desorption component is selected from one or more combinations of sodium pyrophosphate, sodium tripolyphosphate, sodium hexametaphosphate, and EDTA-2Na.

[0017] Furthermore, the porous adsorbent material is activated carbon.

[0018] Furthermore, the enamel restoration material is nano-hydroxyapatite.

[0019] Furthermore, the first porous carrier and / or the second porous carrier are selected from silica or mesoporous silicon materials with different pore sizes.

[0020] Furthermore, the friction matrix is ​​one or more combinations of calcium carbonate and calcium hydrogen phosphate.

[0021] Furthermore, the surfactant is one or more combinations of sodium lauroyl sarcosinate and sodium cocoyl glutamate.

[0022] Furthermore, the sweetener is one or more combinations of xylitol and erythritol.

[0023] Furthermore, the spice is one or more of peppermint oil and cinnamon oil.

[0024] The present invention also provides a method for preparing the above-mentioned teeth whitening composition, comprising the following steps:

[0025] (1) Activation of the carrier: The first porous carrier and the second porous carrier were activated at 105°C for 2 hours and then cooled to room temperature for use.

[0026] (2) Low-temperature loading: The enzymatic membrane-degrading component and the chelating desorption component were dissolved in water respectively. At 25°C, the enzymatic membrane-degrading component was impregnated with the first porous carrier for 2 hours, and the chelating desorption component was impregnated with the second porous carrier for 2 hours. Afterwards, they were vacuum dried and passed through an 80-100 mesh sieve to obtain composite particles 1 and 2. The mass ratio of the enzymatic membrane-degrading component to the first porous carrier was controlled between 1:2 and 1:20, and the mass ratio of the chelating desorption component to the second porous carrier was controlled between 1:2 and 1:20.

[0027] (3) Base material mixing: Add the friction matrix, porous adsorption material and enamel restoration material into the mixer and dry mix for 15 minutes.

[0028] (4) General mixing: Add compound particles 1, compound particles 2, surfactant, sweetener and flavoring to the mixer and mix for 20 minutes until uniform.

[0029] (5) Filling.

[0030] Furthermore, the present invention also protects the use of the composition in the preparation of oral care products for removing extrinsic stains, reducing tooth re-staining, and repairing tooth enamel.

[0031] The core technical principle of this invention lies in "staged synergistic release" and "enzymatic enhancement":

[0032] (a) Phased release mechanism

[0033] This invention achieves the sequential release of each component by designing a porous carrier with significant pore size differences:

[0034] Phase 1 (0-1 minute): The first porous carrier with larger pore size has a fast release rate, and the enzymatic membrane-degrading components are released rapidly (release rate ≥90%), decomposing the acquired membrane on the tooth surface and exposing calcium ion binding sites.

[0035] The second stage (2-3 minutes): The second porous carrier with smaller pore size slowly releases the chelated desorbed components (release rate ≥85%), efficiently chelating calcium ions and breaking the bonds between pigments and teeth.

[0036] The third stage (continues after 2 minutes): As the preceding processes gradually remove the staining layer on the tooth surface, the porous adsorption material (activated carbon) and the enamel repair material (nano-hydroxyapatite) continue to work, adsorbing free pigments and repairing and polishing the enamel surface, reducing its roughness (Ra value can be reduced from 128 nm before treatment to 56 nm), thereby reducing pigment re-attachment (re-staining rate can be reduced from 31% to 15%).

[0037] (ii) Enzyme-enhanced effect

[0038] The acquired membrane is a thin organic film covering the surface of tooth enamel, approximately 0.1-1 micrometer thick, composed of glycoproteins and mucins from saliva. This membrane is not only susceptible to staining by pigments but also physically blocks chelating agents from contacting the enamel surface. The papain or bromelain used in this invention can specifically hydrolyze the protein network within the acquired membrane, breaking it down into peptides and amino acids. This exposes calcium ion binding sites on the enamel surface, allowing the subsequently released chelating agent to effectively chelate calcium ions and cleave pigment-binding bonds.

[0039] (III) The protective effect of porous carriers

[0040] This invention loads the enzymatic and chelating components onto porous silica supports of different pore sizes, achieving not only physical isolation and sequential release of the active components but also preventing inactivation caused by direct contact with abrasives, surfactants, etc. Experiments show that the enzyme activity retention rate of the supported group can reach over 92%, while that of the direct mixing group is only 41.5%.

[0041] Through the synergistic effect of enzymatic hydrolysis, chelation, adsorption, and repair, this invention achieves efficient removal of extrinsic tooth stains with low enamel damage and low restaining rate.

[0042] Compared with the prior art, the present invention has the following beneficial effects:

[0043] (1) Phased synergistic release significantly improves whitening efficiency.

[0044] This invention achieves three-stage time-sequential release through pore size differences. Experimental results show that the pigment removal rate ΔE value of Examples 1-3 reached 12.0-13.0, which is significantly higher than that of Comparative Example 5 (direct mixing group, ΔE=6.1), Comparative Example 6 (enzyme-free group, ΔE=5.5) and Comparative Example 9 (commercial product, ΔE=8.1), confirming the superiority of multi-mechanism phased synergy (P<0.05).

[0045] (2) The porous carrier protects enzyme activity and the product has excellent stability.

[0046] Loading the enzyme-catalyzed components into a porous carrier effectively avoids deactivation caused by direct contact with abrasives and surfactants. Accelerated aging experiments showed that the enzyme activity retention rate of the carrier-loaded group of this invention reached 92.3±2.5%, while that of the direct mixing group was only 41.5±3.2%, and the difference was statistically significant (P<0.05).

[0047] (3) Gentle and does not damage tooth enamel, with high safety.

[0048] Testing showed that the dentin abrasion value (RDA) of Examples 1-3 of this invention was only 50-55, far lower than that of commercially available products (RDA=78) and standard tooth powder (RDA=100). The enamel hardness (HV) after treatment was 342±10, with no significant difference from the untreated value (345±12), while the hardness of commercially available products decreased to 301±11 after treatment. The in vitro mucosal irritation test score was 0, and no adverse reactions were observed in 30 volunteers who used the product continuously for 4 weeks.

[0049] (4) Repairs tooth enamel and significantly reduces the restaining rate.

[0050] The nano-hydroxyapatite restorative material contained in this invention can effectively fill the micropores on the enamel surface and reduce surface roughness (Ra value decreased from 128±6 nm before treatment to 56±3 nm). Restaining experiments showed that the restaining rate of Examples 1-3 was only 13-16%, far lower than that of Comparative Example 8 (31%) without restorative material and commercially available products (27%).

[0051] (5) Non-peroxide mechanism, no risk of irritation

[0052] This invention does not use any peroxide-based bleaching agents, thus avoiding the common side effects of tooth sensitivity and gum irritation associated with traditional bleaching whitening products, and can be safely used for daily oral care. Attached Figure Description

[0053] Figure 1 This is a three-component release kinetic curve of Example 1 of the present invention.

[0054] Figure 2 This is a release kinetics curve for Comparative Example 1 of the present invention.

[0055] Figure 3 This is a release kinetics curve for Comparative Example 2 of the present invention.

[0056] Figure 4 This is a release kinetics curve for Comparative Example 3 of the present invention.

[0057] Figure 5 This is a release kinetics curve for Comparative Example 4 of the present invention. Detailed Implementation

[0058] The present invention will be further described below with reference to specific embodiments and comparative examples. Unless otherwise specified, all contents are weight percentages (wt%).

[0059] Examples 1-3

[0060] The teeth whitening compositions of Examples 1-3 were prepared according to the formulations shown in Table 1 and the preparation methods described below.

[0061] Table 1 Formulation Table for Examples 1-3

[0062]

[0063] In embodiments 1-3 of the present invention:

[0064] The first porous carrier is macroporous silica with an average pore size of approximately 75 nm and a specific surface area of ​​64 m². 2 / g, pore volume 1.2 cm³ 3 / g; the second porous support is made of small-pore silica with an average pore size of approximately 4 nm and a specific surface area of ​​800 m². 2 / g, pore volume 0.8 cm³ 3 / g.

[0065] Preparation method:

[0066] (1) Activation of the carrier: The first porous carrier and the second porous carrier were activated at 105°C for 2 hours and then cooled to room temperature for use.

[0067] (2) Low-temperature loading: The enzyme-catalyzed membrane desorption component and the chelate desorption component were dissolved in water respectively. At 25°C, the enzyme-catalyzed membrane desorption component was impregnated with the first porous carrier for 2 hours, and the chelate desorption component was impregnated with the second porous carrier for 2 hours. After that, they were vacuum dried and passed through an 80-100 mesh sieve to obtain composite particles 1 and 2.

[0068] In a specific design of this invention, the mass ratio of the enzymatic desorption component to the first porous carrier is controlled between 1:2 and 1:20, and the mass ratio of the chelation and desorption component to the second porous carrier is controlled between 1:2 and 1:20. With this specific loading ratio and the aforementioned specific pore volume and specific surface area working synergistically, the active substance can be completely capillarily adsorbed into the internal pores of the porous carrier, and hardly remains free on the system surface. This not only effectively isolates the enzyme activity from the destructive effects of surfactants, but also ensures a strictly controlled, staged release effect upon subsequent contact with water.

[0069] (3) Base material mixing: Add the friction matrix, porous adsorption material and enamel restoration material into the mixer and dry mix for 15 minutes.

[0070] (4) General mixing: Add compound particles 1, compound particles 2, surfactant, sweetener and flavoring to the mixer and mix for 20 minutes until uniform.

[0071] (5) Filling.

[0072] Release performance test of carriers with different pore sizes

[0073] Using Example 1 as a comparative sample, the release performance of carriers with different pore sizes was tested through Comparative Examples 1-4.

[0074] Comparative Example 1: The two carriers have the same pore size (10-20 nm).

[0075] Comparative Example 2: The pore sizes of the two carriers are similar (first carrier 15-30 nm, second carrier 10-20 nm).

[0076] Comparative Example 3: The carrier pore sizes are configured in reverse (first carrier 2-10 nm, second carrier 20-80 nm).

[0077] Comparative Example 4: Both carriers have relatively large pore sizes (100-150 nm).

[0078] Test method: 1.0 g of each comparative product was placed in simulated saliva at 37℃ and pH=6.8. Samples were taken at different time points, and the concentrations of papain and bromelain in the solution were determined by high performance liquid chromatography (HPLC); the concentration of pyrophosphate was determined by ion chromatography; and the release rate-time curves of each component were plotted. Figure 2-5 As shown.

[0079] Results: A clear staged release behavior can only be achieved when the enzyme and chelating agent are loaded onto carriers with significantly different pore sizes (such as the scheme of this invention). When the pore sizes are the same or small, the staged release phenomenon weakens or disappears.

[0080] Performance comparison of different formulations or preparation methods

[0081] Using Example 1 as a comparative sample, performance comparisons were conducted using Comparative Examples 5-9, showing different formulations or preparation methods:

[0082] Comparative Example 5: Compared with Example 1, the enzyme and chelating agent were not loaded onto a carrier and were directly mixed.

[0083] Comparative Example 6: Compared with Example 1, no enzymatic membrane degradation component was added.

[0084] Comparative Example 7: No chelating desorption component was added compared to Example 1.

[0085] Comparative Example 8: No enamel restoration material was added compared to Example 1.

[0086] Comparative Example 9: Commercially available regular teeth whitening powder.

[0087] Performance Tests and Results

[0088] 1. Release kinetics test (Example 1)

[0089] 1.0 g of the product prepared in Example 1 was placed in simulated saliva (37 ℃, pH=6.8), and samples were taken at 0, 0.5, 1, 1.5, 2, 2.5, and 3 minutes. The concentrations of papain and bromelain in the solution were determined by high-performance liquid chromatography (HPLC); the concentration of pyrophosphate was determined by ion chromatography; and the turbidity change of hydroxyapatite was measured by ultraviolet spectrophotometry. Release rate-time curves for each component were plotted, as shown below. Figure 1 As shown.

[0090] Results: The release rate of the enzymatic component reached 90% within 0-1 minute; the release rate of the chelated component reached 85% within 1-2 minutes; and the release rate of the repair material peaked after 2 minutes. This confirmed the three-stage release mechanism. It should be noted that since the porous adsorbent material and the enamel repair material (nano-hydroxyapatite) are unloaded free particles in this system, the "peak release rate after 2 minutes" observed in the test essentially refers to the peak value of their effective contact, dispersion, and adsorption / remineralization response rate at the enamel interface. Within the first two minutes, due to the tight physical barrier of the exogenous organic acquired membrane and the deep-bound pigments on the tooth surface, the free restorative material cannot effectively reach and deposit in the enamel micropores. After two minutes, as the previously loaded enzymatic and chelating components strictly follow the time sequence to completely hydrolyze and chelate the aforementioned organic contamination layer, the micropores on the enamel surface are fully exposed. This causes the free nano-hydroxyapatite in the system to undergo a large-scale interfacial response and rapidly deposit and fill the gap in a very short time. In objective tests, this results in a perfect staged synergistic restorative effect where the release rate peaks after two minutes.

[0091] 2. Enzyme activity retention rate test

[0092]

[0093] Conclusion: Porous carriers can effectively protect enzyme activity, and the difference is statistically significant (P<0.05).

[0094] 3. Enamel surface roughness and dentin wear value (RDA) test

[0095]

[0096] Conclusion: The hydroxyapatite-containing examples significantly reduced the surface roughness of tooth enamel, and the RDA value was much lower than that of commercially available products, indicating better gentleness (P<0.05).

[0097] 4. Enamel hardness test

[0098]

[0099] Conclusion: This invention causes no significant damage to tooth enamel and is significantly safer than commercially available products (P<0.05).

[0100] 5. Pigment removal rate test (ΔE value)

[0101]

[0102] Conclusion: Examples 1-3 showed the highest ΔE values, indicating that the synergistic effect of the system significantly improved the teeth whitening effect (P<0.05).

[0103] 6. Recoloring Test

[0104]

[0105] Conclusion: Examples containing repair materials can significantly reduce the recoloring rate, indicating that the repair effect of hydroxyapatite can effectively reduce pigment redeposition (P<0.05).

[0106] 7. Oral safety test

[0107] In vitro mucosal stimulation test: The stimulation score of all samples in the examples was 0 (no stimulation).

[0108] Human trial: 30 volunteers used the sample of the example for 4 consecutive weeks, and no adverse reactions such as oral mucosal irritation or gingival sensitivity occurred.

[0109] In summary, the teeth whitening composition with phased synergistic release provided by the present invention is significantly superior to the prior art in terms of pigment removal rate, restaining inhibition, and enamel repair, and has good safety, demonstrating significant technological progress and application value.

Claims

1. A teeth whitening composition with staged synergistic release, characterized in that, By weight percentage, it consists of the following components: 0.5%-2% of enzymatic membrane-degrading components, 0.5%-5% of chelating desorption components, 5%-10% of porous adsorption materials, 5%-10% of enamel restoration materials, 45%-65% of abrasive matrix, 5%-10% of the first porous carrier, 5%-10% of the second porous carrier, 3%-5% of surfactants, 5%-10% of sweeteners, and 0.5%-2% of flavorings; The pore size of the first porous carrier is 50-100 nm, and the pore size of the second porous carrier is 2-20 nm; The enzymatic membrane desorption component is loaded on the first porous support; the chelation desorption component is loaded on the second porous support; The composition achieves phased, time-sequential release through the pore size difference between the first porous carrier and the second porous carrier.

2. The composition according to claim 1, characterized in that, The enzymatic membrane degradation component is selected from one or more combinations of papain, bromelain, and lysozyme.

3. The composition according to claim 1, characterized in that, The chelating and desorption components are selected from one or more combinations of sodium pyrophosphate, sodium tripolyphosphate, sodium hexametaphosphate, and EDTA-2Na.

4. The composition according to claim 1, characterized in that, The porous adsorption material is activated carbon; and / or, the enamel repair material is nano-hydroxyapatite.

5. The composition according to claim 1, characterized in that, The first porous carrier and / or the second porous carrier are selected from silica or mesoporous silica materials with different pore sizes; wherein, the specific surface area of ​​the first porous carrier is 30-150 m². 2 / g, pore volume 0.8-1.5 cm³ 3 / g; the specific surface area of ​​the second porous carrier is 600-1000 m². 2 / g, pore volume 0.5-1.0 cm³ 3 / g.

6. The composition according to claim 1, characterized in that, The friction matrix is ​​one or more of calcium carbonate and dicalcium phosphate; the surfactant is one or more of sodium lauroyl sarcosinate and sodium cocoyl glutamate; the sweetener is one or more of xylitol and erythritol; and the flavoring is one or more of peppermint oil and cinnamon oil.

7. The composition according to claim 1, characterized in that, The composition is tooth powder.

8. A method for preparing the teeth whitening composition according to any one of claims 1-7, characterized in that, Includes the following steps: (1) Activation of the carrier: The first porous carrier and the second porous carrier were activated at 105°C for 2 hours and then cooled to room temperature for use. (2) Low temperature loading: The enzyme-catalyzed membrane desorption component and the chelating desorption component are dissolved in water respectively. At 25°C, the enzyme-catalyzed membrane desorption component is immersed in the first porous carrier for 2 hours, and the chelating desorption component is immersed in the second porous carrier for 2 hours. After that, they are vacuum dried and passed through an 80-100 mesh sieve to obtain composite particles 1 and composite particles 2. (3) Base material mixing: The friction matrix, the porous adsorption material and the enamel restoration material are put into the mixer and dry-mixed for 15 minutes; (4) Total mixing: Add the composite particles 1, composite particles 2, surfactant, sweetener and flavoring to the mixer and mix for 20 minutes until homogeneous; (5) Filling.

9. The preparation method according to claim 8, characterized in that, In step (2), the mass ratio of the enzymatic membrane desorption component to the first porous carrier is 1:2 to 1:20; the mass ratio of the chelation desorption component to the second porous carrier is 1:2 to 1:

20.

10. The use of the composition according to any one of claims 1-7 in the preparation of an oral care product for removing extrinsic stains, reducing tooth re-staining, and repairing tooth enamel.

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